Insights image for “The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling.” Chhinder P. Sodhi1,2, Peter Wipf3, Yukihiro Yamaguchi1,2, William B. Fulton1,2, Mark Kovler1,2, Diego F. Niño1,2, Qinjie Zhou1,2, Emilyn Banﬁeld1, Adam D. Werts3, Mitchell R. Ladd1,2, Rachael H. Buck4, Karen C. Goehring4, Thomas Prindle Jr1,2, Sanxia Wang1,2, Hongpeng Jia1,2, Peng Lu1,2 and David J. Hackam 1,2
Pediatric Research _#####################_ ; https://doi.org/10.1038/s41390-020-01184-w
The human milk oligosaccharides (HMO) present in breast milk block the binding of Gram-negative bacteria to the complex of TLR4 and MD2 by competitive inhibition, thus blocking the activation of TLR4 and preventing NEC. Formula does not contain HMO. Thus Gram-negative bacteria can bind to the TLR4-MD2 complex, (1) activating NF-κB that leads to cell death, and (2) increases the expression of TLR4 in the cell membrane.1 Formula
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REFERENCE 1. Sodhi, C. P. et al. The human milk oligosaccharides 2’-fucosyllactose and 6’-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling. Pediatr. Res. https://doi.org/10.1038/s41390020-0852-3 (2020).
NF-κβ Cell death
No NEC Gram negative bacteria
D.J.H. is supported by R01GM078238 and R01DK083752 from the National Institutes of Health, and this research was funded in part by a Sponsored Research Grant to D.J.H. from Abbott Nutrition.
Statement of consent: Samples were obtained de-identiﬁed under IRB 00094036 and consent was not required.
1 Division of General Pediatric Surgery, Johns Hopkins University and Johns Hopkins Children’s Center, Baltimore, MD 21287, USA; 2Department of Surgery, Johns Hopkins University and Johns Hopkins Children’s Center, Baltimore, MD 21287, USA; 3Department of Chemistry, University of Pittsburgh, Pittsburgh, PA, USA and 4Abbott Nutrition, A Division of Abbott Laboratories, Columbus, OH, USA Correspondence: David J. Hackam ([email protected]
Received: 17 September 2020 Accepted: 17 September 2020
© International Pediatric Research Foundation, Inc. 2020